Real-time COVID Detection: Innovative Breathalyzer Sniffs Out Diseases, May Also Detect Lung Disease and Cancer.

With each breath, humans exhale more than 1,000 distinct molecules, resulting in a unique chemical fingerprint or “breathprint” that is rich in clues about what is happening inside the body.

For decades, scientists have sought to harness this information, turning to dogs, mice, and even bees to sniff out cancer, diabetes, tuberculosis, and more.

Scientists from CU Boulder and the National Institute of Standards and Technology (NIST) have made an important leap forward in the quest to diagnose the disease using exhaled breath, reporting that a new laser-based artificial intelligence (AI)-powered ventilator can detect COVID-19 in real time with excellent accuracy.

The results were published April 5 in Journal of Respiration Research.

“Our results show the promise of breath analysis as an alternative, rapid, non-invasive test for COVID-19 and highlight its remarkable potential for diagnosing diverse conditions and disease states,” said first author Qizhong Liang, PhD. Candidate in JILA and the Department of Physics at CU Boulder. JILA is a partnership between CU Boulder and NIST.

The interdisciplinary team of physicists, biochemists and biologists is now turning its focus to a wide range of other diseases in hopes that the “frequency comb alcohol analyzer” born from Nobel Prize winning technology From CU – could revolutionize medical diagnosis.

“There is a real and predictable future in which you can go to the doctor and have your breath measured along with your height and weight…or you can blow into a mouthpiece built into your phone and get information about your health in real time,” said senior author Jun Ye, a JILA fellow and professor. Physics Assistant at CU Boulder.”The possibilities are endless.”

A fledgling COVID collaboration

Since 2008, Ye’s lab has reported that a technique called frequency comb spectroscopy—essentially using laser light to distinguish one molecule from another—can identify biomarkers of disease in human breath.

The technology lacks sensitivity and, more importantly, the ability to link specific molecules to disease states, so they never test them to diagnose disease.

But Yi’s team has since improved the sensitivity a thousandfold, making it possible to detect trace molecules at the parts-per-trillion level. They also harnessed the power of artificial intelligence.

“The molecules increase or decrease in concentrations when they are associated with certain health conditions,” Liang said. “Machine learning analyzes this information, identifies patterns and develops criteria that we can use to predict prognosis.”

With SARS-CoV-2 ravaging across the country and frustration growing about the long response times of existing tests, it’s time to test the system on people. As a physicist, Ye has never worked with human subjects, so he sought help from CU’s BioFrontiers Institute, an interdisciplinary biomedical research center that was heading up a COVID-testing program on campus.

Non-invasive, fast, and chemical-free

Between May 2021 and January 2022, the research team collected breath samples from 170 University of Colorado Boulder students who, in the past 48 hours, had undergone a polymerase chain reaction (PCR) test, either by providing a saliva or nasal sample.

Half of them tested positive, the other half negative. (For safety reasons, the volunteer participants came to an outdoor parking lot on campus, blew off a sample collection bag and left it for the lab tech waiting at a safe distance.)

Overall, the process took less than an hour from compilation to result.

Compared to PCR, the gold standard COVID test, the breathalyzer matched results 85% of the time. For medical diagnoses, an accuracy of 80% or greater is considered “excellent.”

The researchers suspect that the accuracy would likely have been higher if the breath and saliva/nasal swab samples were collected at the same time.

Unlike a nasal swab, the breathalyzer is non-invasive. And unlike a saliva sample, users are not required to refrain from eating, drinking, or smoking before using it. It does not require costly chemicals to break down the sample. The new test could be used on unconscious individuals.

But there is still a lot to learn, Ye said.

With one breath, we can collect a lot of data points from you, but then what? We only understand how few particles associated with specific conditions,” Ye said.

Build a smaller breathing analyzer

Today, the “alcoholometer” consists of a complex of lasers and mirrors the size of a banquet table.

A sample of breath is inserted through a tube where a laser shoots invisible infrared light at thousands of different frequencies. Dozens of tiny mirrors bounce light back and forth across the molecules so many times that the light eventually travels 1.5 miles.

Because each type of molecule absorbs light differently, breath samples with different molecular makeup cast distinct shadows. The machine can distinguish between those different shades or patterns of absorption, boiling millions of data points down — in the case of COVID — to a simple positive or negative point, in a matter of seconds.

Efforts are already underway to miniaturize such systems to a chip scale, allowing for what Liang envisions as “real-time monitoring of self-health on the go.” The possibility does not end there.

said molecular biologist and co-author Leslie Lenwand, chief scientific officer at BioFrontiers and co-author of the study.

Elsewhere, scientists are working to develop Atlas of the human psyche, which maps every molecule in human exhalation and links them to health outcomes. Liang hopes to contribute to such efforts with an extensive collection of breath samples.

Meanwhile, the team is collaborating with pediatric and respiratory specialists at the Anschwitz University Medical Campus to explore how a breath analyzer can not only diagnose diseases but also enable scientists to better understand them, offering hints about immune responses, nutritional deficiencies and other factors that can contribute or disease exacerbation.

“If you think about dogs, they have evolved over thousands of years to smell many different things with remarkable sensitivity,” Ye said. “We’re just at the beginning of our laser-based nose training. The more we teach it, the smarter it gets.”